Wales captain Alun Wyn Jones faces an absence of "weeks not days" after being injured on international duty.
The 35-year-old Ospreys lock, Test rugby's most capped player, has had a scan on the knee he injured during Wales' Autumn Nations Cup victory against Italy last Saturday.
"He's had a scan and we're assessing what that means," said Ospreys head coach Toby Booth.
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"From a time out point of view it's going to be weeks not days, which is disappointing for everybody."
Jones will miss the start of the Ospreys' European Challenge campaign against Castres Olympique on Saturday.
Wales' Six Nations opener is against Ireland in Cardiff on February 7, just over eight weeks away.
The absence of the 152-times capped Jones would be a huge blow for Wales head coach Wayne Pivac, who struggled for wins during his first year in charge.
Pivac managed only three Test victories in 2020, against Italy twice and Georgia, and oversaw Wales' worst Six Nations campaign since 2007.
On the length of Jones' possible absence, Booth said: "I can't answer that question because I don't know until we get the full picture on the scan and the recommendations of the consultants.
"Wales will be involved as he was in their charge if you like, and there's a few people who need to compare notes.
"But we play a tough sport and unfortunately it's part of the business we're in."